Synthesis, in silico, in vitro evaluation of furanyl- and thiophenyl-3-phenyl-1H-indole-2-carbohydrazide derivatives as tubulin inhibitors and anticancer agents
Issued Date
2024-01-01
Resource Type
ISSN
26328682
Scopus ID
2-s2.0-85195854978
Journal Title
RSC Medicinal Chemistry
Rights Holder(s)
SCOPUS
Bibliographic Citation
RSC Medicinal Chemistry (2024)
Suggested Citation
Saruengkhanphasit R., Ngiwsara L., Lirdprapamongkol K., Chatwichien J., Niwetmarin W., Eurtivong C., Kittakoop P., Svasti J., Ruchirawat S. Synthesis, in silico, in vitro evaluation of furanyl- and thiophenyl-3-phenyl-1H-indole-2-carbohydrazide derivatives as tubulin inhibitors and anticancer agents. RSC Medicinal Chemistry (2024). doi:10.1039/d4md00210e Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98881
Title
Synthesis, in silico, in vitro evaluation of furanyl- and thiophenyl-3-phenyl-1H-indole-2-carbohydrazide derivatives as tubulin inhibitors and anticancer agents
Corresponding Author(s)
Other Contributor(s)
Abstract
Twenty-one new indole derivatives comprising of seven furanyl-3-phenyl-1H-indole-carbohydrazide derivatives and fourteen thiophenyl-3-phenyl-1H-indole-carbohydrazide derivatives were synthesised and biologically evaluated for their microtubule-destabilising effects, and antiproliferative activities against the National Cancer Institute 60 (NCI60) human cancer cell line panel. Among the derivatives, 6i showed the best cytotoxic activity exhibiting selectivity for COLO 205 colon cancer (LC50 = 71 nM), SK-MEL-5 melanoma cells (LC50 = 75 nM), and MDA-MB-435 (LC50 = 259 nM). Derivative 6j showed the strongest microtubule-destabilising effect. Both 6i and 6j were able to induce G2/M cell cycle arrest and apoptosis in MDA-MB-231 triple-negative breast cancer cells. Molecular docking simulation results suggested that these derivatives inhibit tubulin by binding at the colchicine site. The calculated molecular descriptors showed that the most potent derivatives have acceptable pharmacokinetic profiles and are favourable for oral drug administration.